Thromb Haemost 2001; 85(06): 1048-1054
DOI: 10.1055/s-0037-1615962
Review Article
Schattauer GmbH

Fine Mapping of Inhibitory Anti-factor V Antibodies Using Factor V C2 Domain Mutants

Identification of Two Antigenic Epitopes Involved in Phospholipid Binding
Tomonori Izumi
1   Division of Hematology, Departments of Medicine and Pathology, Duke University Medical Center, Durham, North Carolina, USA
,
Suhng Wook Kim*
1   Division of Hematology, Departments of Medicine and Pathology, Duke University Medical Center, Durham, North Carolina, USA
,
Anne Greist
2   Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana, USA
,
Sandra Macedo-Ribeiro
3   Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany
,
Pablo Fuentes-Prior
3   Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany
,
Wolfram Bode
3   Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, Germany
,
William H. Kane
1   Division of Hematology, Departments of Medicine and Pathology, Duke University Medical Center, Durham, North Carolina, USA
,
Thomas L. Ortel
1   Division of Hematology, Departments of Medicine and Pathology, Duke University Medical Center, Durham, North Carolina, USA
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Publikationsverlauf

Received 28. August 2000

Accepted after revision 11. Januar 2001

Publikationsdatum:
12. Dezember 2017 (online)

Summary

Hemorrhagic factor V inhibitors frequently bind to the second C-type (C2) domain of factor V and interfere with phospholipid binding. To define specific residues recognized by inhibitors from four patients (one bovine thrombin-induced and three spontaneous antibodies), epitope mapping was performed using recombinant human factor V lacking most of the B-type domain (FV des B) and alanine-substituted mutants within the C2 domain (FV des B C2 mutants). FV des B C2 mutants located in the region between Lys2060 and Glu2069 were resistant to inhibition by three IgG preparations including the bovine thrombin-induced antibody in both prothrombinase and phospholipid-binding assays. In contrast, mutations at Lys2087 and Lys2092/ Glu2096 were significantly resistant to inhibition by the fourth IgG preparation in both prothrombinase and phospholipid-binding assays. These results confirm interference of phospholipid binding by hemorrhagic factor V inhibitors and support the role(s) of these residues in phospholipid binding.

Presented in part at the 41st Annual Meeting of the American Society of Hematology, New Orleans, Louisiana, December 3–7, 1999

* Department of Clinical Laboratory Science, College of Health Sciences, Korea University, Korea;


Instituto de Biologia Molecular de Barcelona, CSIC, Spain


 
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